2, 7-diaminothioxanthol dioxide and 2, 7-diaminethioxanthone dioxide



- a period of about 1 hour.

Patented July 20, 1954 2,7-DIAM'ENOTHIUXANTHOL DIOXIDE AND2,7-DIAMENETHIOXANTHONE DIOXIDE Edward Delbert Amstutz, Bethlehem. Pa..assignor to The Wm. S. Merrell (Jompany, Cincinnati, Ohio, a corporationoi Delaware No Drawing. Original application July 23, 1946,

Serial No. 685,787.

Divided and this application December 6, 1950, Serial No. 193,584

3 (llaims.

The present invention relates to new chemical compounds and moreparticularly to 2,7-diaminothioxanthone dioxide and2,7-diaminothioxanthencl dioxide. These compounds characterized by twoaminophenyl groups linked together by a carbonyl or hydroxymethylenegroup and a sulfone (S02) group along with amino derivatives of the sameare of value for combatting bacterial infections. The compounds may berepresented by the following formula:

x Hm um where X is selected from the group consisting of carbonyl andhydroxymethylene.

EXAMPLE I 2,7-dz'aminothioscanthone dioxide This compound isconveniently prepared in a four-step process as follows:

(a) 5-nitro-2-(p-nitrothiophenory) benzaldehyde.-A hot solution of5-nitro-2-chlorobenzaldehyde (0.14 mole) and 350 ml. of alcohol isprepared and diluted with 140 ml. of Warm water. p-Nitro-thiophenoxide(0.15 mole) is then added with stirring. The mixture is heated to refluxfor about 1 hour, and after cooling the precipitate is filtered andWashed successively with cold alcohol and Water. The yield of 5-nitro-2-(pnitrothiophenoxy) benzaldehyde is high.

(2)) Cyclz'ection of 5-m'tro-2-(p-nitrot7iiophenom benzaZdehyde.-The dryproduct obtained step (a) (9.12 mole) is added with stirring toconcentratedsuliuric acid (370 ml.) over The mixture is slowly heated to69 C. and is maintained at this temperature for mins, whereupon it iscooled poured onto chipped ice (about 580 grains). The precipitate whichseparates is filtered, washed with water, and dried. The product is amixture of 2,'Zdinitrothioxanthone and 2,7- dinitrothioxanthene, whichis not separated.

(c) 2,7-diniirothiorcnthone dioxide-The product from step ('b) is heatedto reflux with a mixture of glacial acetic acid (736 ml.) and 30%hydrogen peroxide (193 grams) for 4 hours. The reaction mixture iscooled and the precipitate is filtered and washed successively withwater, sodium bicarbonate solution, and again with water. The yield ofdry 2,7-dinitrothioxanthone dioxide is high.

(d) 2,7-diaminoihioxanthone dioxide-A suspension of2,7-dinitrothioxanthone dioxide (0.1

mole) in glacial acetic acid ml.) is prepared and is heated to 80 on asteam bath. A solution of stannous chloride dihydrate (0.75 mole) inglacial acetic acid (450 ml.) saturated with gaseous hydrogen chlorideis added gradually with stirring. After the addition of all the stannouschloride, heating is continued for about 2 hours at 80 C. The mixture isnow cooled to 10 C. and the precipitate is removed by filtration andwashed thoroughly with water. The washed filter cake is suspended inwater made alkaline by the addition of sodium hydroxide solution, andthe orange colored diamino compound is then filtered with suction,washed with water and dried. The crude product is heated to reflux withabout 500 ml. of acetone. The hot mixture is filtered and the clearyellow filtrate concentrated to a volume of about ml. Upon cooling thepure 2,7-diaminothioxanthone dioxide, M. P. 2935-298" (3., separates asa yellow crystalline powder in good yield.

EXAMPLE II 2,7-diamz'nothiuxanthenol dioxide 2,7-dinitrothioxanthonedioxide (0.1 mole) in 80% acetic acid (400 ml.) is heated gradually toreflux with zinc dust (1.0 equivalent) which has previously been washedwith hot dilute hydrochloric acid. The initial phase of the reduction isspontaneously exothermic and external heat is not required. The totalreflux period is about 1 hour with the liquid becoming a pale yellow incolor. The boiling mixture is then filtered to remove the excess zincand the hot filtrate is diluted with 1500 ml. of hot water. On cooling,a colorless precipitate separates which is suction filtered, and washedwith sodium bicarbonate solution followed by Water. The yield of dryproduct, M. P. 204 C., is high. After recrystallization (Darco) fromabout 400 m1. of alcohol, the product melts at 212 C. withdecomposition.

The compounds of the present invention contain two reactive amino groupsand the hydrogen atoms in these groups may be replaced by various typesof radicals. They may be acetylated, for example, by reaction withacetic anhydride in glacial acetic acid to form the respectivediacetamido derivatives. With a large excess of acetic anhydride the2,7-diaminothioxanthenol dioxide product forms the9-acetoxy-2,'7-diacetamido derivative. Other derivatives including thealdehyde sulioxylate and bisulfite derivatives along with certainheterocyclic derivatives are disclosed and claimed in my copendingapplications. The present application is a division 3 of my priorapplication Serial No. 685,787 filed July 23, 1946, now abandoned.

I claim: 1. Compounds represented by the formula:

Where X is selected from the group consisting of carbonyl andhydroxymethylene.

2. The product, 2,7-diaminothioxanthone dioxide.

3. The product, 2,7-diaminothioxantheno1 dioxide.

References Cited in the file of this patent UNITED STATES PATENTS NumberName Date 2,149,335 Dahlen Mar. 7, 1939 Number Name Date 2,338,516 Kernet a1. Jan. 4, 1944 2,592,529 Amstutz Apr. 15, 1952 FOREIGN PATENTSNumber Country Date 253,714 Germany June 1, 1911 420,743 Great BritainNov. 29, 1934 618,121 Germany Sept. 2, 1935 OTHER REFERENCES Perkin eta1., Beilstein (Handbuch, 4th ed), v01. 18,. p. 613 (1934). V

Sachs, Beilstein (Handbuch, 4th ed.) v01. 18, p. 614 (1934).

Mauss, Chemotherapy, Fiat Rev. of Ger. Science, Office of Military Govt.for Ger. 1939-

1. COMPOUNDS REPRESENTED BY THE FORMULA: